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Updated: Apr 11, 2026

Intracerebroventricular Delivery of Gut-Derived Microbial Metabolites in Freely Moving Mice
Published on: June 2, 2022
Infant gut microbiomes contribute to metabolic states that impact brain function
Firas S Midani1,2, Do-Hun Lee3,4, Younghye Moon3,4
1Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
Insights
Early infant gut microbiome alterations are linked to cognitive deficits. Microbiota interventions in mice restored normal behavior, suggesting a potential therapeutic target for neurodevelopmental disorders.
Area of Science:
- Microbiome research
- Neurodevelopmental disorders
- Metabolic pathways
Background:
- Gut microbiome alterations are linked to neurodevelopmental disorders.
- Causal mechanisms and therapeutic strategies are not well-defined.
Purpose of the Study:
- To investigate the causal role of early-life gut microbiomes in neurodevelopment.
- To explore microbiota-based interventions for cognitive deficits.
Main Methods:
- Transferred infant gut microbiomes to mice to assess behavioral and metabolic phenotypes.
- Utilized fecal microbiota transplantation and rationally designed microbial consortia for intervention.
- Analyzed fecal amino acid concentrations and replicated findings in a second cohort.
Main Results:
- Early-life microbiomes from infants with later cognitive deficits induced adverse phenotypes in mice.
- Microbiota interventions, including fecal microbiota transplant, rescued behavioral deficits in mice.
- Lower fecal amino acid concentrations were observed in low-scoring infants, with replication in a second cohort.
Conclusions:
- Early-life microbiome composition causally influences neurodevelopment and behavior.
- Microbiota-based interventions show promise for treating cognitive deficits.
- Amino acid metabolism is a key pathway linking the gut microbiome to cognitive outcomes.
Abstract:
Alterations in the gut microbiome are associated with neurodevelopmental disorders, but causal mechanisms and therapeutic strategies remain undefined. Here, we demonstrate that human infant microbiomes isolated during the first six months of life drive behavioral impairments in mice and that microbiota-based interventions restore mice to normal behavior. Early-life microbiomes from twelve infants who later exhibited cognitive deficits at 2 years old (low-scoring) transferred adverse metabolic, brain, and behavioral phenotypes to mice, in contrast to microbiomes from twenty-three cognitively typical or high-scoring infants. Deficits in mice were rescued by fecal microbiota transplant from high-scoring infants or a rationally designed consortium that promoted amino acid levels. We confirmed lower fecal amino acid concentrations in low-scoring infants and replicated the association between early-life microbiome composition and cognitive outcomes in a second geographically independent infant cohort. Altogether, we discovered an early-life microbiome-mediated metabolic state causally linked to cognitive deficits and amenable to microbial intervention.
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